Ultrastructural studies on Entamoeba histolytica have been carried out mostly with trophozoites cultured for many years. Under these conditions, the availability of nutrients and the absence of environmental stimuli may switch off some phenotypic characteristics of the parasite. As a result, virulence of E. histolytica diminishes with prolonged culture passages, and the ability to form cysts disappears in axenically maintained trophozoites. The present analysis by transmission electron microscopy of trophozoites recovered from experimental amebic liver lesions in hamsters revealed two types of cytoplasmic changes. On the one hand, the number of peripheral electron dense granules significantly increased in amebas obtained from liver lesions 15 min and 6h after inoculation. On the other hand, large cytoplasmic vesicles with a microfibrillar content appeared in trophozoites cultured from 72 or 96 h hepatic lesions. With fluorescence microscopy, a chitin-like material was identified in these vesicles by reactivity with calcofluor M2R. Ultrastructurally, these cytoplasmic components resemble the encystation vesicles of Entamoeba invadens and Giardia lamblia. The release of large amounts of electron dense granules, known to contain collagenase activity, probably contributes to degrade extracellular matrix components during tissue invasion. In addition, under the conditions mentioned above, amebas form encystation-like vesicles in an incomplete process of differentiation into cysts, which are the resistant form of the parasite.